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Abstract

The spatial and temporal regulation of calcium signaling in neuronal growth cones is essential for axon guidance. In growth cones, the endoplasmic reticulum (ER) is a significant source of calcium signals. However, it is not clear whether the ER is remodeled during motile events to localize calcium signals in steering growth cones. The expression of the ER-calcium sensor, stromal interacting molecule 1 (STIM1) is necessary for growth cone steering toward the calcium-dependent guidance cue BDNF, with STIM1 functioning to sustain calcium signals through store-operated calcium entry. However, STIM1 is also required for growth cone steering away from semaphorin-3a, a guidance cue that does not activate ER-calcium release, suggesting multiple functions of STIM1 within growth cones (Mitchell et al., 2012). STIM1 also interacts with microtubule plus-end binding proteins EB1/EB3 (Grigoriev et al., 2008). Here, we show that STIM1 associates with EB1/EB3 in growth cones and that STIM1 expression is critical for microtubule recruitment and subsequent ER remodeling to the motile side of steering growth cones. Furthermore, we extend our data in vivo, demonstrating that zSTIM1 is required for axon guidance in actively navigating zebrafish motor neurons, regulating calcium signaling and filopodial formation. These data demonstrate that, in response to multiple guidance cues, STIM1 couples microtubule organization and ER-derived calcium signals, thereby providing a mechanism where STIM1-mediated ER remodeling, particularly in filopodia, regulates spatiotemporal calcium signals during axon guidance.

Item Type:	Article
Authors/Creators:	Pavez, MP and Thompson, AC and Arnott, HJ and Mitchell, CB and D'Atri, I and Don, EK and Chilton, EK and Scott, EK and Lin, JY and Young, KM and Gasperini, RJ and Foa, L
Keywords:	axon guidance, calcium, endoplasmic reticulum, cell motility, microtubule, optogenetic, STIM1
Journal or Publication Title:	Journal of Neuroscience
Publisher:	Society for Neuroscience
ISSN:	0270-6474
DOI / ID Number:	https://doi.org/10.1523/JNEUROSCI.2496-18.2019
Copyright Information:	Copyright 2019 by the Society for Neuroscience
Related URLs:	UTAS Profile: Lin, JY UTAS Profile: Young, KM UTAS Profile: Gasperini, RJ Google Scholar: Foa, L UTAS Profile: Foa, L
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